Down-Regulation of IgE and IgG4 Antibodies to Tetanus Toxoid and Diphtheria Toxoid by Covaccination with Cellular Bordetella pertussis Vaccine

Abstract

Pertussis (P) toxin acts as adjuvant for IgE formation against simultaneously administered Ags in animal models. P vaccination may also have an adjuvant impact on IgE formation against coadministered diphtheria (D) and tetanus (T) Ags in humans. Sera of 103 D-T-P-immunized and 319 D-T-immunized children aged 2 years were analyzed for IgE, IgG4, and IgG to D and T (radioallergosorbent test), total IgE and IgE against common inhalant allergens (CAP radioallergosorbent test fluoroenzyme immunoassay). Fewer D-T-P- than D-T-immunized children had sera positive for T-IgE (12.6 vs 53.6%, p < 0.001), T-IgG4 (71.6 vs 89.2%, p < 0.001), D-IgE (31.0 vs 70.5%, p < 0.001), and D-IgG4 (85.2 vs 93.4%, p = 0.039). Suppression of T-IgE was not dependent on the cutoff chosen for a positive test result, but was dependent on the proportion of D-T immunizations given with P. The risk for sensitization to common environmental allergens did not differ (odds ratio 0.953, 95% confidence interval 0.815–1.114). No significant differences between D-T- and D-T-P-immunized children were found with regard to T-IgG or D-IgG. In summary, IgE and IgG4 (but not IgG) serum levels to coadministered D- and T-Ags are suppressed among P-immunized children as compared with nonimmunized children. These results suggest that the presence of a microbial product during Ag exposure can down-regulate an IgE/IgG4 response in humans.

Assessing vaccine effectiveness of publicly funded vaccination programs in Queensland

“…In contrast, vaccination with wP, which also contains PT, down-regulates IgE production (170). This is believed to be due to bacterial cell wall antigens such as lipopolysaccharide (LPS) which are present in wP, absent in aP, and which are thought to have T helper 1 (Th1) adjuvantising/Th2 down-regulating properties (170). Unlike natural infection neither wP nor aP vaccines induce pertussis-specific IgA production, thought to be an important contributor to mucosal protection against pertussis (164).…”

“…By the time they are 12 months old, children who received primary vaccination with aP still demonstrated a mixed Th2/Th1 response to pertussis toxins although global Th2 bias appears to normalize (181). Booster doses of aP vaccine given to older children primed with aP vaccine in infancy boost the Th2 skewed response to pertussis and tetanus toxins, but do not appear to promote IgE production to common food and aero-allergens (170,171,180).…”

“…Infection with B.pertussis provokes a complex and as yet incompletely understood immune Pertussis toxin (PT), a component of both aP and wP vaccines is recognized as having strong IgEadjuvantising properties (170). aP vaccination stimulates serum IgE production to both pertussis toxins and co-administered antigens such as tetanus and diphtheria toxoids (121,165,171).…”

“…Booster doses of aP further enhance the IgE response (171). In contrast, vaccination with wP, which also contains PT, down-regulates IgE production (170). This is believed to be due to bacterial cell wall antigens such as lipopolysaccharide (LPS) which are present in wP, absent in aP, and which are thought to have T helper 1 (Th1) adjuvantising/Th2 down-regulating properties (170).…”

“…A temporary maturational delay in Th1 function, more specifically in the production of IFNγ, may occur after aP vaccination (121). Th2 skewing of infant immune responses following priming with aP vaccines may result from the combined effect of the Th2-biased phenotype at birth, together with the presence of alum (in some aP products) and PT which both have Th2-stimulating properties, and the absence of cell wall-derived Th1-stimulating ligands in aP vaccines (170,179,180).…”